研究者詳細 - 豊國　伸哉

論文 - 豊國　伸哉

分割表示 1,236 件中 801 - 820 件目／全件表示 >>

Target genes in free radical-induced carcinogenesis

Toyokuni S

SFRR: PROCEEDINGS OF THE XII BIENNIAL MEETING OF THE SOCIETY FOR FREE RADICAL RESEARCH INTERNATIONAL 頁： 181 - 185 2004年

Target genes and genomic areas in free radical-induced carcinogenesis

Toyokuni, S; Akatsuka, S; Shirase, T; Than, TA

FREE RADICAL BIOLOGY AND MEDICINE 36 巻頁： S29 - S29 2004年

Target genes in free radical-induced carcinogenesis 査読有り

S Toyokuni

SFRR: PROCEEDINGS OF THE XII BIENNIAL MEETING OF THE SOCIETY FOR FREE RADICAL RESEARCH INTERNATIONAL 頁： 181 - 185 2004年

記述言語：英語掲載種別：研究論文（国際会議プロシーディングス）出版者・発行元：MEDIMOND PUBLISHING CO

Ferric nitrilotriacetate-induced renal carcinogenesis presents an intriguing model demonstrating what happens if repeated Fenton reaction occurs in vivo. We have asked a question whether there is any target gene in this carcinogenesis model. With a genetic approach, we found that p15 and p16 tumor suppressor genes are one of the major targets. Furthermore, allelic loss of p16 was present as early as three weeks after the start of the experiments. In this model, alterations in expressional levels of several genes were also observed by differential display analysis. Among them, annexin 2 was overexpressed in renal cell carcinoma, and was regulated by oxidative stress. Persistent operation of this adaptive mechanism plays a role in the proliferation and metastasis of oxidative stress-induced cancer.

Web of Science

researchmap

Formation of acrolein-derived 2'-deoxyadenosine adduct in an iron-induced carcinogenesis model. 査読有り国際誌 Open Access

Kawai Y, Furuhata A, Toyokuni S, Aratani Y, Uchida K

The Journal of biological chemistry 278 巻 ( 50 ) 頁： 50346 - 54 2003年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Biological Chemistry

Acrolein is a representative carcinogenic aldehyde found ubiquitously in the environment and formed endogenously through oxidation reactions, such as lipid peroxidation and myeloperoxidase-catalyzed amino acid oxidation. It shows facile reactivity toward DNA to form an exocyclic DNA adduct. To verify the formation of acrolein-derived DNA adduct under oxidative stress in vivo, we raised a novel monoclonal antibody (mAb21) against the acrolein-modified DNA and found that the antibody most significantly recognized an acrolein-modified 2′-deoxyadenosine. On the basis of chemical and spectroscopic evidence, the major antigenic product of mAb21 was the 1,N6-propano-2′ -deoxyadenosine adduct. The exposure of rat liver epithelial RL34 cells to acrolein resulted in a significant accumulation of the acrolein-2′ -deoxyadenosine adduct in the nuclei. Formation of this adduct under oxidative stress in vivo was immunohistochemically examined in rats exposed to ferric nitrilotriacetate, a carcinogenic iron chelate that specifically induces oxidative stress in the kidneys of rodents. It was observed that the acrolein-2′-deoxyadenosine adduct was formed in the nuclei of the proximal tubular cells, the target cells of this carcinogenesis model. The same cells were stained with a monoclonal antibody 5F6 that recognizes an acrolein-lysine adduct, by which cytosolic accumulation of acrolein-modified proteins appeared. Similar results were also obtained from myeloperoxidase knockout mice exposed to the iron complex, suggesting that the myeloperoxidase-catalyzed oxidation system might not be essential for the generation of acrolein in this experimental animal carcinogenesis model. The data obtained in this study suggest that the formation of a carcinogenic aldehyde through lipid peroxidation may be causally involved in the pathophysiological effects associated with oxidative stress.

DOI： 10.1074/jbc.M309057200

Restoration of fertility in infertile mice by transplantation of cryopreserved male germline stem cells. 査読有り国際誌 Open Access

Kanatsu-Shinohara M, Ogonuki N, Inoue K, Ogura A, Toyokuni S, Shinohara T

Human reproduction (Oxford, England) 18 巻 ( 12 ) 頁： 2660 - 7 2003年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Human Reproduction

Background: The development of a spermatogonial transplantation technique has provided new possibilities for the treatment of male infertility. Previous studies have shown that spermatogonial stem cells could reinitiate spermatogenesis after cryopreservation and reintroduction into the seminiferous tubules of infertile recipient males, and this raised the possibility of banking frozen stem cells for male infertility treatment. It remains unknown, however, whether germ cells from freeze-thawed stem cells are fertile, leaving the possibility that the procedure compromises the integrity of the stem cells. Methods and results: Dissociated mouse testis cells were cryopreserved and transplanted into infertile recipient testes. The freeze-thawed testis cell populations contained higher concentrations of stem cells than fresh testis cell populations. Offspring were obtained from freeze-thawed stem cells transplanted into infertile males, and fertility restoration was more efficient in immature (5-10 days old) than in mature (6-12 weeks old) recipients. However, offspring were also obtained from infertile adult recipients using in-vitro microinsemination. Conclusions: This first successful application of frozen stem cell technology in the production of offspring by spermatogonial transplantation suggests the superiority of immature recipients for clinical applications. Thus, the combination of cryopreservation and transplantation of stem cells is a promising approach to overcome male infertility.

DOI： 10.1093/humrep/deg483

Effects of the phenolic contents of Mauritian endemic plant extracts on promoter activities of antioxidant enzymes. 査読有り国際誌

Toyokuni S, Tanaka T, Kawaguchi W, Fang NR, Ozeki M, Akatsuka S, Hiai H, Aruoma OI, Bahorun T

Free radical research 37 巻 ( 11 ) 頁： 1215 - 24 2003年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Free Radical Research

Oxidative stress has been associated with a variety of pathologic conditions in humans. Increasing the transcriptional activities of antioxidant enzymes might be a strategy to prevent oxidative stress-associated diseases such as atherosclerosis and cancer. In the present paper, we studied the effects of extracts from 12 Mauritian endemic plants on the promoter activities of antioxidant enzymes; Cu, Zn-superoxide dismutase (Cu,Zn-SOD), Mn-superoxide dismutase (Mn-SOD), catalase, and glutathione dismutase (GPx). The levels of total phenolic compounds, total flavonoids, and proanthocyanidins were measured. Four luciferase expression vectors (pGL3-Basic) with promoter region of each enzyme were constructed, transfected to COS7 cells followed by an exposure to each extract (25 μg/ml, 24 h, non-toxic dose). Thereafter, luciferase activities were evaluated in comparison with a control luciferase vector with a herpes simplex virus thymidine kinase promoter. Mauritian endemic plants contained high amounts of total phenols, flavonoids and proanthocyanidins. Total phenols and flavonoids were proportionally associated with Cu,Zn-SOD promoter activity, whereas they were inversely correlated with catalase promoter activity. These results suggest that the chemopreventive potentials of the extracts might reside in their abilities to modulate the expression of the antioxidant enzyme genes.

DOI： 10.1080/10715760310001598150

Edaravone, a novel free radical scavenger, protects myocardium against oxidative stress after cardioplegic arrest

Yamazaki, K; Miwa, S; Toyokuni, S; Horii, T; Unimonh, O; Sasahashi, N; Takaba, K; Komeda, M

CIRCULATION 108 巻 ( 17 ) 頁： 175 - 175 2003年10月

Edaravone, a novel free radical scavenger, protects myocardium against oxidative stress after cardioplegic arrest 国際誌

Yamazaki, K, Miwa, S, Toyokuni, S, Horii, T, Unimonh, O, Sasahashi, N, Takaba, K, Komeda, M

CIRCULATION 108 巻 ( 17 ) 頁： 175 - 175 2003年10月

Novel aspects in free radical chemistry and biology 査読有り国際誌

Toyokuni, S

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS 417 巻 ( 1 ) 頁： 2 - 2 2003年9月

Long-term proliferation in culture and germline transmission of mouse male germline stem cells. 査読有り国際誌

Mito Kanatsu-Shinohara, Narumi Ogonuki, Kimiko Inoue, Hiromi Miki, Atsuo Ogura, Shinya Toyokuni, Takashi Shinohara

Biology of reproduction 69 巻 ( 2 ) 頁： 612 - 6 2003年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SOC STUDY REPRODUCTION

Spermatogenesis is a complex process that originates in a small population of spermatogonial stem cells. Here we report the in vitro culture of spermatogonial stem cells that proliferate for long periods of time. In the presence of glial cell line-derived neurotrophic factor, epidermal growth factor, basic fibroblast growth factor, and leukemia inhibitory factor, gonocytes isolated from neonatal mouse testis proliferated over a 5-month period (>10(14)-fold)and restored fertility to congenitally infertile recipient mice following transplantation into seminiferous tubules. Long-term spermatogonial stem cell culture will be useful for studying spermatogenesis mechanism and has important implications for developing new technology in transgenesis or medicine.

DOI： 10.1095/biloreprod.103.017012

Web of Science

PubMed

researchmap

Long-term proliferation in culture and germline transmission of mouse male germline stem cells

Kanatsu-Shinohara M, Ogonuki N, Inoue K, Miki H, Ogura A, Toyokuni S, Shinohara T

BIOLOGY OF REPRODUCTION 69 巻 ( 2 ) 頁： 612 - 616 2003年8月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Biology of Reproduction

Spermatogenesis is a complex process that originates in a small population of spermatogonial stem cells. Here we report the in vitro culture of spermatogonial stem cells that proliferate for long periods of time. In the presence of glial cell line-derived neurotrophic factor, epidermal growth factor, basic fibroblast growth factor, and leukemia inhibitory factor, gonocytes isolated from neonatal mouse testis proliferated over a 5-month period (>1014-fold) and restored fertility to congenitally infertile recipient mice following transplantation into seminiferous tubules. Long-term spermatogonial stem cell culture will be useful for studying spermatogenesis mechanism and has important implications for developing new technology in transgenesis or medicine.

DOI： 10.1095/biolreprod.103.017012

Web of Science

Scopus

PubMed

Involvement of death receptor Fas in germ cell degeneration in gonads of Kit-deficient Wv/Wv mutant mice. 査読有り国際誌 Open Access

Sakata S, Sakamaki K, Watanabe K, Nakamura N, Toyokuni S, Nishimune Y, Mori C, Yonehara S

Cell death and differentiation 10 巻 ( 6 ) 頁： 676 - 86 2003年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Cell Death and Differentiation

Kit and its ligand stem cell factor (SCF) play a fundamental role in hematopoiesis, melanogenesis and gametogenesis. Homozygous Wv mutant mice with a mutation in kit show abnormalities in these cell lineages. Fas is a member of the death receptor family inducing apoptosis. In this study, we generated double-mutant mice (Wv/Wv:Fas-/-) and analyzed histologically their reproductive organs. In testes and ovaries of the double-mutant mice, testicular germ cells and oocytes were detected, respectively, whereas the same-aged Wv/Wv mice contained neither cells. In addition, inhibition of Kit signals by administration of anti-Kit mAb, which induces degeneration of testicular germ cells in vivo in wild-type mice, did not cause degeneration in Fas-deficient mice. In testicular germ cells of Wv/Wv mutant mice, an increase of Fas expression was observed in spermatogonia. Further, in vitro treatment with SCF was shown to downregulate Fas on fibroblasts expressing exogenous Kit through activation of PI3-kinase/Akt. All the results clearly indicate that Fas-mediated apoptosis is involved in germ cell degeneration accompanied by defects in Kit-mediated signals, and Kit signaling negatively regulates Fas-mediated apoptosis in vivo.

DOI： 10.1038/sj.cdd.4401215

Evidence for oxidative stress in NSAID-induced colitis in IL10-/- mice. 国際誌

Seiko Narushima, Douglas R Spitz, Larry W Oberley, Shinya Toyokuni, Toshio Miyata, Carol A Gunnett, Garry R Buettner, Juan Zhang, Hanan Ismail, Richard G Lynch, Daniel J Berg

Free radical biology & medicine 34 巻 ( 9 ) 頁： 1153 - 66 2003年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

The goal of this study was to evaluate for evidence of oxidative stress in colonic inflammation in a novel model of inflammatory bowel disease, nonsteroidal anti-inflammatory drug- (NSAID-) treated interleukin-10-deficient (IL10(-/-)) mice. IL10(-/-) and wild-type (wt) mice were treated with a nonselective NSAID (piroxicam, 200 ppm in the diet) for 2 weeks to induce colitis, and parameters for oxidative stress in the colonic tissues were evaluated. Mean chemiluminescence enhanced with lucigenin in the colons from IL10(-/-) mice treated with piroxicam was more than 5-fold higher than that of the control wt group. Chemiluminescence was inhibited with diphenylethylene iodinium, but not allopurinol, indomethacin, or N-omega-nitro-L-arginine, indicating that flavin-containing enzymes were the source of the reactive oxygen species. Colonic aconitase activity in NSAID-treated IL10(-/-) mice decreased to 50% of the activity of control mice. There was no difference in the total glutathione levels in the colonic mucosa among the groups; however, glutathione disulfide levels were approximately 2-fold greater in the colon of NSAID-treated IL10(-/-) mice as compared with control groups. Immunohistochemistry studies of colons from NSAID-treated IL10(-/-) mice demonstrated intense staining with two antibodies that recognize advanced glycation endproducts formed through glycation and oxidation: anticarboxymethylysine and antipentosidine. The epithelial cells and lamina propria cells in the colons of NSAID-treated IL10(-/-) mice showed immunostaining with antinitrotyrosine, indicating the presence of reactive nitrogen species. Colonic epithelium of IL10(-/-) mice with colitis showed moderate immunostaining for 8-hydroxy-2'-deoxyguanosine in the nuclei. NSAID-treated IL10(-/-) mice treated with diphenylene idodonium chloride (DPI), an irreversible inhibitor of flavoprotein enzymes, experienced significantly reduced inflammation. Taken together, these results strongly indicate the presence of oxidative stress in the inflammatory bowel disease in NSAID-treated IL10(-/-) mice and suggests a role for oxidative stress in the pathophysiology of this model of inflammatory bowel disease.

PubMed

researchmap

Evidence for oxidative stress in NSAID-induced colitis in IL10(-/-) mice

Narushima S, Spitz DR, Oberley LW, Toyckuni S, Miyata T, Gunnett CA, Buettner GR, Zhang J, Ismail H, Lynch RG, Berg DJ

FREE RADICAL BIOLOGY AND MEDICINE 34 巻 ( 9 ) 頁： 1153 - 1166 2003年5月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Free Radical Biology and Medicine

The goal of this study was to evaluate for evidence of oxidative stress in colonic inflammation in a novel model of inflammatory bowel disease, nonsteroidal anti-inflammatory drug- (NSAID-) treated interleukin-10-deficient (IL10-/-) mice. IL10-/- and wild-type (wt) mice were treated with a nonselective NSAID (piroxicam, 200 ppm in the diet) for 2 weeks to induce colitis, and parameters for oxidative stress in the colonic tissues were evaluated. Mean chemiluminescence enhanced with lucigenin in the colons from IL10-/- mice treated with piroxicam was more than 5-fold higher than that of the control wt group. Chemiluminescence was inhibited with diphenylethylene iodinium, but not allopurinol, indomethacin, or N-ω-nitro-L-arginine, indicating that flavin-containing enzymes were the source of the reactive oxygen species. Colonic aconitase activity in NSAID-treated IL10-/- mice decreased to 50% of the activity of control mice. There was no difference in the total glutathione levels in the colonic mucosa among the groups; however, glutathione disulfide levels were approximately 2-fold greater in the colon of NSAID-treated IL10-/- mice as compared with control groups. Immunohistochemistry studies of colons from NSAID-treated IL10-/- mice demonstrated intense staining with two antibodies that recognize advanced glycation endproducts formed through glycation and oxidation: anticarboxymethylysine and antipentosidine. The epithelial cells and lamina propria cells in the colons of NSAID-treated IL10-/- mice showed immunostaining with antinitrotyrosine, indicating the presence of reactive nitrogen species. Colonic epithelium of IL10-/- mice with colitis showed moderate immunostaining for 8-hydroxy-2′-deoxyguanosine in the nuclei. NSAID-treated IL10-/- mice treated with diphenylene idodonium chloride (DPI), an irreversible inhibitor of flavoprotein enzymes, experienced significantly reduced inflammation. Taken together, these results strongly indicate the presence of oxidative stress in the inflammatory bowel disease in NSAID-treated IL10-/- mice and suggests a role for oxidative stress in the pathophysiology of this model of inflammatory bowel disease. © 2003 Elsevier Inc.

DOI： 10.1016/S0891-5849(03)00065-0

Web of Science

Scopus

PubMed

Functional assessment of self-renewal activity of male germline stem cells following cytotoxic damage and serial transplantation. 査読有り国際誌 Open Access

Kanatsu-Shinohara M, Toyokuni S, Morimoto T, Matsui S, Honjo T, Shinohara T

Biology of reproduction 68 巻 ( 5 ) 頁： 1801 - 7 2003年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Biology of Reproduction

Spermatogenesis is dependent on a small population of stem cells. Although stem cells are believed to expand infinitely, there is little functional evidence regarding whether spermatogonial stem cells can increase in their number. Using the spermatogonial transplantation technique, we evaluated the proliferative potential of spermatogonial stem cells in two models of regeneration. After busulfan injection to deplete stem cells, the surviving stem cells were able to expand by at least 15.8-fold within 2 mo. On the other hand, a serial transplantation study indicated that one transplanted stem cell was able to expand by 3.8-and 12-fold within 2 and 4 mo, respectively. These results provide direct functional evidence for the expansion of stem cells and establish the basis for further characterization of the stem cell self-renewal process.

DOI： 10.1095/biolreprod.102.012575

Intermittent microwave irradiation facilitates antigen-antibody reaction in Western blot analysis

TOYOKUNI Shinya, KAWAGUCHI Waka, AKATSUKA Shinya, HIROYASU Makoto, HIAI Hiroshi

Pathology international 53 巻 ( 4 ) 頁： 259 - 261 2003年4月